News beyond our pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2023)

Eosinophil-directed biologic therapies have proven beneficial in patients with eosinophilic asthma but not chronic obstructive pulmonary disease (COPD). In order to explain these differences in treatment response, Cabrera López et al (Am J Respir Crit Care Med 2023;208:155-62; https://doi.org/10.1164/rccm.202301-0149OC) characterized the surface protein patterns of peripheral eosinophils in patients with asthma and COPD. Higher proportions of inflammatory eosinophils (iEos) and IL-5 receptor levels were observed in patients with asthma as compared to patients, smokers without COPD, or healthy control individuals. Notably, the latter 3 groups exhibited similar proportions of resident eosinophils (rEos) and iEos. In total, these results identify circulating eosinophil subtypes that distinguish patients with asthma and COPD, which may explain their differential responses to eosinophil-directed therapies. We asked corresponding author Carlos Cabrera López, MD, PhD, from the Respiratory Service, University Hospital of Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain, to comment on the study. He writes, “The existence of 2 different subtypes of eosinophils could explain the poor results of biological therapies in COPD and the difference in blood and tissue eosinophilia in specific diseases.” Tauber et al (J Exp Med 2023;220:e20230570; https://doi.org/10.1084/jem.20230570) combined whole-tissue imaging and genome-wide single-cell RNA sequencing datasets to explore the phenotypical and functional heterogeneity of mast cells at steady state in both humans and mice. Two distinct mast cell subpopulations were identified in mice with distinct origins. Connective tissue-type mast cells were present in virtually all organs, and their presence was independent of bone marrow progenitors. In contrast, mucosal-type mast cells were restricted to the lamina propria of the gastrointestinal tract and were renewed by bone marrow progenitors. Notably, enhanced natural diversity of mast cells was observed in humans as at least 6 distinct mast cell states were identified across 12 organs. In total, this comprehensive analysis has provided a pan-organ overview of mast cell diversity in both mice and humans. We asked corresponding author Nicolas Gaudenzio, PhD, from the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) and Genoskin, Toulouse, France, to comment on the study. He writes, “Very little is known about mast cell ontogeny, renewal dynamics, and heterogeneity across species. This study is intended to serve as an initial foundation for researchers to collaborate and aggregate their own single-cell datasets, thereby forming a more extensive database encompassing mast cell subtypes/states in both healthy and diseased states.” In order to understand the roles of innate mononuclear phagocytic system (MPS) cells in local nasal allergic responses, Voskamp et al (J Exp Med 2023;220:e20221111; https://doi.org/10.1084/jem.20221111) combined single-cell proteomic and transcriptomic profiling of nasal immune cells following repeated intranasal exposure to house dust mite. Following challenge, allergic patients exhibited enhanced infiltration of inflammatory monocytes and proallergic gene expression in resident type-2 conventional dendritic cells (cDC2s). Conversely, infiltration of myeloid-derived suppressor cells and enrichment of tolerogenic genes in cDC2s were observed. Collectively, these findings highlight the changes in innate MPS cell populations that underlie local nasal allergic responses.Enhanced infiltration of inflammatory monocytes Enhanced infiltration of inflammatory monocytes We asked corresponding author Hermelijn H. Smits, PhD, from the Department of Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands, to comment on the study. She writes, “We observed that nasal innate immune cells from patients with allergic rhinitis responded to allergen provocation with a proinflammatory activity, while nasal innate immune cells from nonallergic individuals responded to allergen provocation with a tolerogenic activity. This is very interesting, as it may suggest that not only inflammatory, but also tolerogenic responses to allergens have been imprinted depending on individual’s disease state and environmental conditions.” Consumption of energy-dense, fiber-poor foods in bursts (termed “feast diet”) is a common social eating behavior. Siracusa et al (Nat Immunol 2023;24:1473-86; https://doi.org/10.1038/s41590-023-01587-x) identified metabolic and immunologic changes that occur in the gastrointestinal tract following such iterative short-term dietary changes. Each feast was associated with transient mucosal immune depression and impaired CD4+ T-cell function due to dysregulation of the intestinal microbiota. Subsequently, higher susceptibility to systemic bacterial infections was observed. Importantly, re-introduction of a fiber-rich diet restored both mucosal and systemic CD4+ T-cell immunity. Collectively, these findings identify that transient immune depression and risk of pathogenic infection are opportunity costs associated with energy-dense feasts. Image Attribution: See page for author, Public domain, via Wikimedia Commons “Good Food display”: https://commons.wikimedia.org/wiki/File:Good_Food_Display_-_NCI_Visuals_Online.jpg.Opportunity costs associated with energy-dense feasts Opportunity costs associated with energy-dense feasts In order to better understand the molecular processes underlying reactivation of memory T cells, Onrust-van Schoonhoven et al (Sci Immunol 2023;8:eadg3917; https://doi.org/10.1126/sciimmunol.adg3917) examined epigenomic drivers of rapid recall in primary human memory TH2 cells. After identifying distinct transcriptional modules linked to rapid recall, the authors identified epigenomic priming in effector loci of resting memory TH2 cells that were not present in naive CD4+ T cells. Multiple epigenetic mechanisms at the levels of transcription, chromatin accessibility, and 3-dimensional genome organization allowed for rapid transcriptional activation of recall genes. Finally, overactivation of primed recall responses was observed in resting memory TH2 cells derived from patients with asthma. Overall, these findings demonstrate memory-specific changes in both the 1-dimensional and 3-dimensional chromatin landscape that mediate rapid recall in memory TH2 cells.Rapid transcriptional activation of recall genesNews items were written by medical writer Jared Travers, MD, PhD. Rapid transcriptional activation of recall genes News items were written by medical writer Jared Travers, MD, PhD.